Investigations>
>Going
for genesOn
September 21, in a determined effort to attack a phalanx of common
and debilitating diseases through its genetic underbelly, an army
of mice, patient samples, and geneticists invaded the newly constructed
Martin Boyer Laboratories. On the fifth floor of the former Billings
Hospital, the labs were created to take the war on inflammatory
bowel disease (IBD) to a new front, by going after their inherited
origins through the genes of families with multiple cases of IBD
and by testing the effects of those suspect genes in mouse models.
Although lobbying for the space and designing and building the
center took more than two years and required nearly $4 million
in financial support, the researchers say that the space, and
the kinds of work that it allows, was worth the wait.

"I
know of no other laboratory quite like this in the world," says
Joseph B. Kirsner, PhD'42, the Louis Block distinguished service
professor of medicine and author of the first scientific paper,
in 1948, on the inheritance of IBD. Kirsner and gastroenterology
researcher Eugene B. Chang, MD'76-the Martin Boyer professor of
medicine and the new labs' director-were instrumental in pulling
together financial backing for the project, including support
from the Boyer family, the Gastrointestinal Research Foundation,
and others.

Inflammatory
bowel disease is a broad term for two painful conditions known
as Crohn's disease and ulcerative colitis. Led by Kirsner and
Stephen Hanauer, U of C physicians have been pioneers in improving
care, testing new therapies, and searching for a cure since the
1930s. The staff cares for more than 5,000 patients with IBD,
including many families with a predisposition to IBD. But despite
years of study of the disorders' epidemiology, biochemistry, and
immunology, the cause-how genes, lifestyle, and environment interact
to trigger uncontrolled inflammation-remains unknown.

Two
Boyer Lab researchers, human geneticist Judy Cho and molecular
immunologist Averil Ma, will use genetic tools-including information
from the newly completed Human Genome Project-to unravel the complicated
events that initiate these disorders and to develop more specific
therapies to treat the disease, not just the symptoms.

The
inflammatory bowel diseases are not simple, single-gene disorders,
and the researchers expect to find multiple genes, in the range
of seven to nine separate but perhaps interrelated genes that
increase a person's risk for IBD. Two years ago, Cho led a team
that performed the largest, most comprehensive genome-wide study
ever done of patients with inflammatory bowel disease. The team
identified regions on chromosomes 1, 3, and 4 that appear to contain
genes that could trigger the disease's onset. They also confirmed
the role of one previously localized gene named IBD1, near the
center of chromosome 16, that appears to act in concert with the
disease gene on chromosome 1.

While
Cho looks for clues in patients' DNA, Ma works with mice, and
their three-day-old embryonic stem cells, to "interrogate" how
specific genes that may be involved in IBD work. His sections
of the lab consist of two tightly controlled areas for sensitive
tissue-culture research. One room is devoted to manipulating the
embryonic stem cells to generate gene-altered mice; the other
room is used for studies of the mice's immune response to various
stimuli, and how altered genes can affect the immune response
to infections and the process of inflammation. Ma is particularly
interested in the role of substances that affect the immune response,
and how the body regulates its response to these potent molecules.

The
new research space and equipment will save time, energy, and money,
says Ma. Before the lab opened, he had to send members of his
team to Atlanta to perform certain essential experiments, waiting
for results before arranging follow-up tests-an expensive, slow,
and inefficient process. Now, he says, "We should be able to make
much more rapid progress."

"The
center is committed to making a difference in the lives of people
with IBD," says Chang. "It's the crucial next step in the long
battle with this disease."